scholarly journals Toxicity Evaluation of Long-Term Topical Application of Recombinant Human Keratinocyte Growth Factor-2 Eye Drops on Macaca Fascicularis

2021 ◽  
Vol 12 ◽  
Author(s):  
Le Li ◽  
Lijia Li ◽  
Qi Chen ◽  
Xuanxin Yang ◽  
Qi Hui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Topical Application ◽  
Macaca Fascicularis ◽  
Keratinocyte Growth Factor ◽  
Sodium Fluorescein ◽  
Epithelial Tissue ◽  
High Dose ◽  
Eye Drops ◽  
Human Keratinocyte

Recombinant human keratinocyte growth factor-2 (rhKGF-2), an effective agent for the regeneration of epithelial tissue, was found to have great potential for use in treatments of corneal diseases that involve corneal epithelial defects. Furthermore, the safety of long-term and high-dose external use of KGF-2 eye drops in rabbits has been well established previously. The aim of this study is to determine the safe dose range and target organs for toxicity of rhKGF-2 eye drops in Macaca fascicularis (M. fascicularis). The M. fascicularis animals were administered with different doses of rhKGF-2 eye drops (125, 500, and 2000 μg/ml) for four consecutive weeks, followed by a 2 week recovery period. No significant differences in weight, electrocardiogram characteristics, blood and urine indexes, pathology, and bone marrow cells were detected among the animals in different groups. The corneas of some animals in the middle- and high-dose groups showed fluorescence when stained with sodium fluorescein, and then the staining disappeared on days 28 and 42. Anti-rhKGF-2 antibodies were detected in a small number of animals in the high-dose group, and their level decreased after rhKGF-2 withdrawal. No neutralizing antibodies were detected. The result demonstrated that there was no obvious adverse reaction when topical application of rhKGF-2 eye drops at the dosage of 125 or 500 μg/ml on the M. fascicularis. This study is of great significance for the future clinical transformation of rhKGF-2 eye drops.

scholarly journals The Effect of Long-Term Low-Dose Atropine on Refractive Progression in Myopic Australian School Children

2021 ◽  
Vol 10 (7) ◽  
pp. 1444
Author(s):  
William Myles ◽  
Catherine Dunlop ◽  
Sally A. McFadden
Keyword(s):  
Low Dose ◽  
High Dose ◽  
Eye Drops ◽  
Myopia Progression ◽  
At Risk Children ◽  
Slow Group ◽  
Blue Eyes ◽  
Global Population ◽  
Axial Growth

Myopia will affect half the global population by 2050 and is a leading cause of vision impairment. High-dose atropine slows myopia progression but with undesirable side-effects. Low-dose atropine is an alternative. We report the effects of 0.01% or 0.005% atropine eye drops on myopia progression in 13 Australian children aged between 2 and 18 years and observed for 2 years without and up to 5 years (mean 2.8 years) with treatment. Prior to treatment, myopia progression was either ‘slow’ (more positive than −0.5D/year; mean −0.19D/year) or ‘fast’ (more negative than −0.5D/year; mean −1.01D/year). Atropine reduced myopic progression rates (slow: −0.07D/year, fast: −0.25D/year, combined: before: −0.74, during: −0.18D/year, p = 0.03). Rebound occurred in 3/4 eyes that ceased atropine. Atropine halved axial growth in the ‘Slow’ group relative to an age-matched model of untreated myopes (0.098 vs. 0.196mm/year, p < 0.001) but was double that in emmetropes (0.051mm/year, p < 0.01). Atropine did not slow axial growth in ‘fast’ progressors compared to the age-matched untreated myope model (0.265 vs. 0.245mm/year, p = 0.754, Power = 0.8). Adverse effects (69% of patients) included dilated pupils (6/13) more common in children with blue eyes (5/7, p = 0.04). Low-dose atropine could not remove initial myopia offsets suggesting treatment should commence in at-risk children as young as possible.

scholarly journals A Novel Solid-Phase Site-Specific PEGylation Enhances the In Vitro and In Vivo Biostabilty of Recombinant Human Keratinocyte Growth Factor 1

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e36423 ◽  
Author(s):  
Zhifeng Huang ◽  
Guanghui Zhu ◽  
Chuanchuan Sun ◽  
Jingui Zhang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Solid Phase ◽  
Keratinocyte Growth Factor ◽  
Site Specific ◽  
Human Keratinocyte

scholarly journals Fabrication and Evaluation of Transdermal Microneedles for a Recombinant Human Keratinocyte Growth Factor

2021 ◽  
Vol 18 (1) ◽  
pp. 96-103
Author(s):  
Melbha Starlin CHELLATHURAI ◽  
Vivien WangTing LING ◽  
Vijayarajkumar PALANIRAJAN
Keyword(s):  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Human Keratinocyte

The effects of in vitro methionine oxidation on the bioactivity and structure of human keratinocyte growth factor

1997 ◽  
pp. 299-308 ◽  
Author(s):  
Christopher S. Spahr ◽  
Linda O. Narhi ◽  
James Speakman ◽  
Hsieng S. Lu ◽  
Yueh-Rong Hsu
Keyword(s):  
Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Methionine Oxidation ◽  
Human Keratinocyte

Potential aggregation hot spots in recombinant human keratinocyte growth factor; a computational study

2020 ◽  
Author(s):  
Mansoureh Shahbazi Dastjerdeh ◽  
Mohammad Ali Shokrgozar ◽  
Hamzeh Rahimi ◽  
Majid Golkar
Keyword(s):  
Growth Factor ◽  
Tertiary Structure ◽  
Computational Study ◽  
Keratinocyte Growth Factor ◽  
Native State ◽  
Hydrophobic Residues ◽  
Aggregation Propensity ◽  
State Aggregation ◽  
Human Keratinocyte ◽  
Aggregation Tendency

Abstract Background: Recombinant human keratinocyte growth factor is a highly aggregation-prone therapeutic protein. The high aggregation liability of rhKGF is manifested by loss of the monomeric form of the protein and accumulation of the aggregated species even at moderate temperatures. Here, we analyzed rhKGF for its vulnerability towards aggregation by detection of aggregation-prone regions (APRs) using several sequence-based computational tools including TANGO, SolubiS, ZipperDB, AGGRESCAN, Zyggregator, Camsol, PASTA, SALSA, WALTZ, SODA, Amylpred, AMYPDB, and structure-based tools including Aggrescan3D and molecular dynamics-based spatial aggregation propensity (SAP) algorithm. Results: The sequence-based prediction of APRs in rhKGF indicated that they are mainly located at positions 10-30, 40-60, 61-66, 88-120, and 130-140 which are rich in β-branched aliphatic, hydrophobic, aromatic and Glutamine/Aspargine (Q/N) residues. Mapping on the rhKGF tertiary structure revealed that most of these residues including F16-R25, I43, E45, R47-I56, F61, Y62, N66, L88-E91, E108-F110, A112, N114, T131, and H133-T140 are surface-exposed in the natively folded protein which can promote aggregation without major unfolding event or the conformational change may occur in the oligomers composed of natively folded monomers. The other regions are buried in the native state and their contribution to non-native aggregation is mediated by a preceding unfolding event in the monomeric state of the protein. The structure-based prediction of APRs using SAP tool limited the number of identified APRs to the dynamically-exposed hydrophobic residues including V12, A50, V51, L88, I89, L90, I118, L135, and I139 mediating the native-state aggregation. Conclusion: Our analysis of APRs in rhKGF identified the regions determining the intrinsic aggregation propensity in both folded (native) and unfolded state of the protein. These regions are the candidate positions for engineering the rhKGF sequence to reduce its aggregation tendency.

Sign in / Sign up

Export Citation Format

Share Document